Over the past 25-30 years, tremendous advances have been made in our fundamental understanding of the molecular genetics and biology that underlie the development of human cancer. This enhanced understanding of the critical hallmarks of cancer has led to an accelerated development of novel agents and treatment regimens to treat individual cancers, and an increasing number of new drugs are now being approved by the US Food and Drug Administration each year. However, despite these significant advances, there remain significant challenges to the ultimate clinical efficacy of thes new therapies whether they be cytotoxic chemotherapy, targeted therapy, and/or immunotherapy. In general, once advanced disease is diagnosed, the patient is incurable. As a result, there remains an urgent and critical need to train individuals with specific expertise in cancer therapeutics. It is especially important to train individuals with a solid understanding of basic science concepts who can then more effectively and successfully translate basic laboratory findings to the clinical setting as well as incorporate correlative science in clinical trials, which can subsequently inform the basic science. Unfortunately, there remains an insufficient level of interaction between basic scientists and translational/clinical investigators in large part because the two worlds are so different in their scope and priority. As such, we believe that the training of physician-scientists in both pre-clinical and clinical/translational science will greatly advance the field of cancer therapeutics with the eventual goal of developing novel agents and treatment regimens that can make a real difference in the lives of cancer patients. The successful treatment of human cancer requires an integrated multi- and inter-disciplinary approach. The University of Pittsburgh Cancer Institute (UPCI) and the Division of Hematology-Oncology are deeply committed to developing novel cancer therapeutics that span the entire range of classic cytotoxic chemotherapy agents, targeted therapies, immunologic agents, and biologic agents. This Training Program has brought together an outstanding group of investigators from the Division of Hematology-Oncology and from six other departments of the University of Pittsburgh School of Medicine, and the scientific expertise of the training faculy includes the entire continuum of pre-clinical, translational, and clinical cancer therapeutics research. This group of scientists understands the significance of training physician-scientists and proposes to achieve this goal by accomplishing the following aims: (1) Recruit highly promising medical oncology fellows, who are committed to a career in academic medical oncology relevant to the field of cancer therapeutics (2) Provide specific graduate-level course work to enhance their knowledge in molecular and cell biology, immunology, biochemistry, pharmacology, genetics, and clinical/translational medicine (3) Provide an in-depth exposure to basic research skills by working with well-established mentors who are focused on cancer therapeutics. This proposal is for a Training Program for medical oncology fellows that encompasses the entire range of cancer therapeutics research and includes basic, translational, and clinical science. Three medical oncology fellows will be supported for each year of the Program. This Training Program will focus on 5 defined research areas: (1) Cytotoxic Chemotherapy; (2) Targeted Molecular Therapy; (3) Immunotherapy; (4) Investigating Mechanisms of Chemosensitivity and Resistance; and (5) Clinical Investigations. Each of these research areas is well-represented by the members of our training faculty, and a representative of each research area is on the Executive Committee. The training experience will consist of formal course work, seminars, journal clubs, basic laboratory research, and clinical/translational research. Basic laboratory and translational research will form the bulk of the training experience. Each of the trainees will participate in graduate-level courses on the principles and techniques of cancer drug development, cancer biology, signaling, immunology, biochemistry, cell biology, genetics, and clinical trials, as well as courses on the responsible conduct of research each year, which will provide them with the necessary foundation to develop an academic career focused on cancer therapeutics. The trainees will enter a mentor's laboratory for two years, with an optional third year of training if approved by the Executive Committee. Assessment and evaluation will take place every 4 months and this evaluation will be presented to the Executive Committee. Following the Committee meeting, the trainee meets with the Program Director, at which time, the trainee will be asked to evaluate his/her experience in the mentor's laboratory. A two-page written summary by each trainee evaluating their overall training experience is required at the conclusion of the research fellowship. We anticipate that this feedback from faculty and trainees, respectively, will enhance the overall academic productivity of the program.